A5069069176- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Spectroscopy and Quantum Chemical Studies
- Neuropeptides and Animal Physiology
- Molecular spectroscopy and chirality
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Machine Learning in Materials Science
- Mass Spectrometry Techniques and Applications
- RNA and protein synthesis mechanisms
- thermodynamics and calorimetric analyses
- Enzyme Structure and Function
- SARS-CoV-2 and COVID-19 Research
- Markov Chains and Monte Carlo Methods
- Theoretical and Computational Physics
- Viral gastroenteritis research and epidemiology
University College London
2020-2023
King's College London
2020-2021
University of Oxford
2020
Institute of Advanced Chemistry of Catalonia
2019
Institute for Research in Biomedicine
2019
The determination of drug residence times, which define the time an inhibitor is in complex with its target, a fundamental part discovery process. Synthesis and experimental measurements kinetic rate constants are, however, expensive consuming. In this work, we aimed to obtain times computationally. Furthermore, propose novel algorithm identify molecular design objectives based on ligand unbinding kinetics. We designed enhanced sampling technique accurately predict free-energy profiles...
Bayesian and Maximum Entropy approaches allow for a statistically sound systematic fitting of experimental computational data. Unfortunately, assessing the relative confidence in these two types data remains difficult as several steps add unknown error. Here we propose use validation-set method to determine balance, thus amount fitting. We apply synthetic NMR chemical shift an intrinsically disordered protein. show that gives consistent results even when other methods assess cannot be...
The RNA helicase (non-structural protein 13, NSP13) of SARS-CoV-2 is essential for viral replication, and it highly conserved among the coronaviridae family, thus a prominent drug target to treat COVID-19. We present here structural models dynamics in complex with its native substrates based on thorough analysis homologous sequences existing experimental structures. performed analysed microseconds molecular (MD) simulations, our model provides valuable insights binding ATP ssRNA at atomic...
Patient symptom relief is often heavily influenced by the residence time of inhibitor-target complex. For human muscarinic receptor 3 (hMR3), tiotropium a long-acting bronchodilator used in conditions such as asthma or chronic obstructive pulmonary disease (COPD). The mechanistic insights into this inhibitor remain unclear; specifically, elucidation main factors determining unbinding rates could help develop next generation antimuscarinic agents. Using our novel algorithm, we were able to...
Abstract Bayesian and Maximum Entropy approaches allow for a statistically sound systematic fitting of experimental computational data. Unfortunately, assessing the relative confidence in these two types data remains difficult as several steps add unknown error. Here we propose use validation-set method to determine balance, thus amount fitting. We apply synthetic NMR chemical shift an intrinsically disordered protein. show that gives consistent results even when other methods assess cannot...
ABSTRACT Patient symptom relief is often heavily influenced by the residence time of inhibitor-target complex. For human muscarinic receptor 3 (hMR3), tiotropium a long-acting bronchodylator used in conditions such as asthma or chronic obstructive pulmonary disease (COPD). The mechanistic insights this inhibitor remain unclear, specifically, elucidation main factors determining unbinding rates could help develop next generation antimuscarinic agents. Using our novel algorithm, we were able...
ABSTRACT Having claimed over 1 million lives worldwide to date, the ongoing COVID-19 pandemic has created one of biggest challenges develop an effective drug treat infected patients. Among all proteins expressed by virus, RNA helicase is a fundamental protein for viral replication, and it highly conserved among coronaviridae family. To there no high-resolution structure bound with ATP RNA. We present here structural insights molecular dynamics (MD) simulation results SARS-CoV-2 both in its...
We present here two novel algorithms for simulated tempering simulations, which break the detailed balance condition (DBC) but satisfy skewed to ensure invariance of target distribution. The irreversible methods we are based on Gibbs sampling and concern breaking DBC at update scheme temperature swaps. utilize three systems as a test bed our methods: Markov chain Monte Carlo simulation simple system described by one-dimensional double well potential, Ising model, molecular dynamics...
ABSTRACT The determination of drug residence times, which define the time an inhibitor is in complex with its target, a fundamental part discovery process. Synthesis and experimental measurements kinetic rate constants are, however, expensive, time-consuming. In this work, we aimed to obtain times computationally. Furthermore, propose novel algorithm identify molecular design objectives based on ligand unbinding kinetics. We designed enhanced sampling technique accurately predict free energy...